Structure and function of Escherichia coli endonuclease III.

Abstract

One of the most exciting areas of atomic structural studies on protein-DNA interactions has been the studies on on DNA repair enzymes. The atomic structures of endonuclease III and endonuclease V, a phage T4 enzyme that repairs pyrimidine dimers, are a significant advance, as they provide the first structural information concerning the mechanism by which enzymes can recognize altered bases in DNA. Endonuclease III from Escherichia coli is a DNA repair enzyme with two distinct activities: it is a DNA N-glycosylase that acts upon ring-saturated, ring-rearranged, and ring-contracted pyrimidines and is an AP lyase. The name endonuclease III was originally applied to an activity that nicked heavily UV-irradiated DNA. The enzyme was found to be identical with E. coli x-ray endonuclease, with an endonuclease that cleaves DNA damaged by UV irradiation, osmium tetroxide, x-rays, or acid, and with urea-DNA glycosylase. The identification of endonuclease III with these various other activities is due to the broad substrate specificity of the enzyme. It has been shown to release dihydrothymine, cis- and trans-thymine glycol, urea, methyltartronylurea and 5-hydroxy-5-methylhydantoin, 6-hydroxy-5,6-dihydrothymine, uracil hydrate, and cytosine hydrate from DNA. Endonuclease III has been shown to be an AP lyase rather than a true AP endonuclease; itmore » cleaves the phosphodiester bond adjacent to an AP site by a {beta}-elimination reaction rather than a hydrolytic reaction. The syn stereochemical course of the {beta}-elimination reaction has been defined: the 2{prime}-pro-S hydrogen is abstracted, and a trans {alpha}{beta}-unsaturated aldose is produced.« less